Microvascular Integrity Plays a Role in Graft Survival After Skin Transplantation.

Abstract

Introduction: Every transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combined with mTOR-inhibition has a beneficial effect on the microvascular integrity in murine skin grafts. Methods: The skin of fully MHC-mismatched C57 BL/6 (H2(b)) donors was transplanted into CBA Jri (H2(k)) mice. The animals were divided in several groups and according to their group treated with Clopidogrel, Everolimus or both. Grafts were harvested after 8 days and analyzed by immunohistology. For this purpose the frozen sections were tagged with anti-CD31 and anti-C4d, respectively. Results: Untreated allografts displayed in comparison to isografts a reduced amount of CD31 on postoperative day 8 as well as an increase in C4d. All treated animals showed a significant improvement regarding CD31 [1748,78 ± 155,71 (Clopidogrel) / 1702,83 ± 151,13 (Clopidogrel + Everolimus) vs. 479,68 ± 184,17 (control), n=8, p<0,05] and c4d [248,86 ± 54,73 (Clopidogrel) / 324,45 ± 77,31 (Clopidogrel + Everolimus) vs. 772,40 ± 159,72 (control), n=8, p<0,05]. The skin grafts of animals treated with Clopidogrel and Everolimus survived significantly longer than untreated controls [19.2 ± 4.2 d vs. 12.8 ± 2.4, n= 10, p<0.05]. Conclusions: Clopidogrel alone and in combination with Everolimus substantially improved the microvascular integrity and resulted in extended skin graft survival.